Adjunct Thrombolysis Enhances Brain Reperfusion following Successful Thrombectomy.

OBJECTIVE: This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy. METHODS: This single-center, randomized, double-blind, placebo-controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near-normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra-arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion-weighted magnetic resonance imaging (MRI) and MRI-spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N-acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity. RESULTS: The prevalence of hypoperfusion was 24% with intra-arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04-0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5-1.2] vs 3.2 [1.8-5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91-1.36] vs 1.00 [0.74-1.22], p < 0.0001). INTERPRETATION: There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity. ANN NEUROL 2022;92:860-870.

Review of the main surgical and angiographic-oriented classifications of the course of the internal carotid artery through a novel interactive 3D model.

The course of the internal carotid artery (ICA) and its segment classifications were reviewed by means of a new and freely available 3D interactive model of the artery and the skull base, based on human neuroimages, that can be freely downloaded at the Public Repository of the University of Barcelona (http://diposit.ub.edu/dspace/handle/2445/112442) and runs under Acrobat Reader in Mac and Windows computers and Windows 10 tablets. The 3D-PDF allows zoom, rotation, selective visualization of structures, and a predefined sequence view. Illustrative images of the different classifications were obtained. Fischer (Zentralbl Neurochir 3:300-313, 1938) described five segments in the opposite direction to the blood flow. Gibo-Rothon (J Neurosurg 55:560-574, 1981) follow the blood flow, incorporated the cervical and petrous portions, and divided the subarachnoid course-supraclinoid-in ophthalmic, communicating, and choroidal segments, enhancing transcranial microscopic approaches. Bouthillier (Neurosurgery 38:425-433, 1996) divided the petrous portion describing the lacerum segment (exposed in transfacial procedures and exploration of Meckel's cave) and added the clinoid segment between the proximal and distal dural rings, of interest in cavernous sinus surgery. The Kassam's group (2014), with an endoscopic endonasal perspective, introduces the "paraclival segment," including the "lacerum segment" and part of the intracavernous ICA, and details surgical landmarks to minimize the risk of injury. Other classifications are also analyzed. This review through an interactive 3D tool provides virtual views of the ICA and becomes an innovative perspective to the segment classifications and neuroanatomy of the ICA and surrounding structures.

Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.

BACKGROUND: In 2015, five randomised trials showed efficacy of endovascular thrombectomy over standard medical care in patients with acute ischaemic stroke caused by occlusion of arteries of the proximal anterior circulation. In this meta-analysis we, the trial investigators, aimed to pool individual patient data from these trials to address remaining questions about whether the therapy is efficacious across the diverse populations included. METHODS: We formed the HERMES collaboration to pool patient-level data from five trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA) done between December, 2010, and December, 2014. In these trials, patients with acute ischaemic stroke caused by occlusion of the proximal anterior artery circulation were randomly assigned to receive either endovascular thrombectomy within 12 h of symptom onset or standard care (control), with a primary outcome of reduced disability on the modified Rankin Scale (mRS) at 90 days. By direct access to the study databases, we extracted individual patient data that we used to assess the primary outcome of reduced disability on mRS at 90 days in the pooled population and examine heterogeneity of this treatment effect across prespecified subgroups. To account for between-trial variance we used mixed-effects modelling with random effects for parameters of interest. We then used mixed-effects ordinal logistic regression models to calculate common odds ratios (cOR) for the primary outcome in the whole population (shift analysis) and in subgroups after adjustment for age, sex, baseline stroke severity (National Institutes of Health Stroke Scale score), site of occlusion (internal carotid artery vs M1 segment of middle cerebral artery vs M2 segment of middle cerebral artery), intravenous alteplase (yes vs no), baseline Alberta Stroke Program Early CT score, and time from stroke onset to randomisation. FINDINGS: We analysed individual data for 1287 patients (634 assigned to endovascular thrombectomy, 653 assigned to control). Endovascular thrombectomy led to significantly reduced disability at 90 days compared with control (adjusted cOR 2.49, 95% CI 1.76-3.53; p<0.0001). The number needed to treat with endovascular thrombectomy to reduce disability by at least one level on mRS for one patient was 2.6. Subgroup analysis of the primary endpoint showed no heterogeneity of treatment effect across prespecified subgroups for reduced disability (pinteraction=0.43). Effect sizes favouring endovascular thrombectomy over control were present in several strata of special interest, including in patients aged 80 years or older (cOR 3.68, 95% CI 1.95-6.92), those randomised more than 300 min after symptom onset (1.76, 1.05-2.97), and those not eligible for intravenous alteplase (2.43, 1.30-4.55). Mortality at 90 days and risk of parenchymal haematoma and symptomatic intracranial haemorrhage did not differ between populations. INTERPRETATION: Endovascular thrombectomy is of benefit to most patients with acute ischaemic stroke caused by occlusion of the proximal anterior circulation, irrespective of patient characteristics or geographical location. These findings will have global implications on structuring systems of care to provide timely treatment to patients with acute ischaemic stroke due to large vessel occlusion. FUNDING: Medtronic.

Relevance of blood-brain barrier disruption after endovascular treatment of ischemic stroke: dual-energy computed tomographic study.

BACKGROUND AND PURPOSE: Computed tomographic (CT) high attenuation (HA) areas after endovascular therapy for acute ischemic stroke are a common finding indicative of blood-brain barrier disruption. Dual-energy CT allows an accurate differentiation between HA areas related to contrast staining (CS) or to brain hemorrhage (BH). We sought to evaluate the prognostic significance of the presence of CS and BH after endovascular therapy. METHODS: A prospective cohort of 132 patients treated with endovascular therapy was analyzed. According to dual-energy CT findings, patients were classified into 3 groups: no HA areas (n=53), CS (n=32), and BH (n=47). The rate of new hemorrhagic transformations was recorded at follow-up neuroimaging. Clinical outcome was evaluated at 90 days with the modified Rankin Scale (poor outcome, 3-6). RESULTS: Poor outcome was associated with the presence of CS (odds ratio [OR], 11.3; 95% confidence interval, 3.34-38.95) and BH (OR, 10.4; 95% confidence interval, 3.42-31.68). The rate of poor outcome despite complete recanalization was also significantly higher in CS (OR, 9.7; 95% confidence interval, 2.55-37.18) and BH (OR, 15.1; 95% confidence interval, 3.85-59.35) groups, compared with the no-HA group. Patients with CS disclosed a higher incidence of delayed hemorrhagic transformation at follow-up (OR, 4.5; 95% confidence interval, 1.22-16.37) compared with no-HA patients. CONCLUSIONS: Blood-brain barrier disruption, defined as CS and BH on dual-energy CT, was associated with poor clinical outcomes in patients with stroke treated with endovascular therapies. Moreover, isolated CS was associated with delayed hemorrhagic transformation. These results support the clinical relevance of blood-brain barrier disruption in acute stroke.

Computer Aided Intracranial Aneurysm Treatment Based on 2D/3D Mapping, Virtual Deployment and Online Distal Marker Detection.

PURPOSE: To introduce a computational tool for peri-interventional intracranial aneurysm treatment guidance that maps preoperative planning information from simulation onto real-time X-Ray imaging. METHODS: Preoperatively, multiple flow diverter (FD) devices are simulated based on the 3D mesh of the vessel to treat, to choose the optimal size and location. In the peri-operative stage, this 3D information is aligned and mapped to the continuous 2D-X-Ray scan feed from the operating room. The current flow diverter position in the 3D model is estimated by automatically detecting the distal FD marker locations and mapping them to the treated vessel. This allows to visually assess the possible outcome of releasing the device at the current position, and compare it with the one chosen pre-operatively. RESULTS: The full pipeline was validated using retrospectively collected biplane images from four different patients (5 3D-DSA datasets in total). The distal FD marker detector obtained an average F1-score of 0.67 ( ± 0.224 ) in 412 2D-X-Ray scans. After aligning 3D-DSA + 2D-X-Ray datasets, the average difference between simulated and deployed positions was 0.832 mm ( ± 0.521 mm). Finally, we qualitatively show that the proposed approach is able to display the current location of the FD compared to their pre-operatively planned position. CONCLUSIONS: The proposed method allows to support the FD deployment procedure by merging and presenting preoperative simulation information to the interventionists, aiding them to make more accurate and less risky decisions.

Impact of Balloon Guide Catheters in Elderly Patients Treated with Mechanical Thrombectomy: Insights from the ROSSETTI Registry.

BACKGROUND AND PURPOSE: Several nonrandomized studies have demonstrated the effectiveness of balloon guide catheters in treating patients with anterior circulation large-vessel occlusion. However, their impact on the elderly populations has been underreported. We aimed to analyze the effect of balloon guide catheters in a cohort of elderly patients (80 years of age or older) with anterior circulation large-vessel occlusion. MATERIALS AND METHODS: Consecutive patients from June 2019 to June 2022 were collected from the ROSSETTI Registry. Demographic and clinical data, angiographic endovascular technique, and clinical outcome were compared between balloon guide catheter and non-balloon guide catheter groups. We studied the association between balloon guide catheters and the rate of complete recanalization after a single first-pass effect modified TICI 2c-3, as well as their association with functional independence at 3 months. RESULTS: A total of 808 patients were included during this period, 465 (57.5%) of whom were treated with balloon guide catheters. Patients treated with balloon guide catheters were older, had more neurologic severity at admission and lower baseline ASPECTS, and were less likely to receive IV fibrinolytics. No differences were observed in terms of the modified first-pass effect between groups (45.8 versus 39.9%, P = .096). In the multivariable regression analysis, balloon guide catheter use was not independently associated with a modified first-pass effect or the final modified TICI 2c-3, or with functional independence at 3 months. CONCLUSIONS: In our study, balloon guide catheter use during endovascular treatment of anterior circulation large-vessel occlusion in elderly patients did not predict the first-pass effect, near-complete final recanalization, or functional independence at 3 months. Further studies, including randomized clinical trials, are needed to confirm these results.

Admission systolic blood pressure and effect of endovascular treatment in patients with ischaemic stroke: an individual patient data meta-analysis.

BACKGROUND: Current guidelines for ischaemic stroke treatment recommend a strict, but arbitrary, upper threshold of 185/110 mm Hg for blood pressure before endovascular thrombectomy. Nevertheless, whether admission blood pressure influences the effect of endovascular thrombectomy on outcome remains unknown. Our aim was to study the influence of admission systolic blood pressure (SBP) on functional outcome and on the effect of endovascular thrombectomy. METHODS: We used individual patient data from seven randomised controlled trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, REVASCAT, PISTE, and THRACE) that randomly assigned patients with anterior circulation ischaemic stroke to endovascular thrombectomy (predominantly using stent retrievers) or standard medical therapy (control) between June 1, 2010, and April 30, 2015. We included all patients for whom SBP data were available at hospital admission. The primary outcome was functional outcome (modified Rankin Scale) at 90 days. We assessed the association of SBP with outcome in both the endovascular thrombectomy group and the control group using multilevel regression analysis and tested for non-linearity and for interaction between SBP and effect of endovascular thrombectomy, taking into account treatment with intravenous thrombolysis. FINDINGS: We included 1753 patients (867 assigned to endovascular thrombectomy, 886 assigned to control) after excluding 11 patients for whom SBP data were missing. We found a non-linear association between SBP and functional outcome with an inflection point at 140 mm Hg (732 [42%] of 1753 patients had SBP <140 mm Hg and 1021 [58%] had SBP ≥140 mm Hg). Among patients with SBP of 140 mm Hg or higher, admission SBP was associated with worse functional outcome (adjusted common odds ratio [acOR] 0·86 per 10 mm Hg SBP increase; 95% CI 0·81-0·91). We found no association between SBP and functional outcome in patients with SBP less than 140 mm Hg (acOR 0·97 per 10 mm Hg SBP decrease, 95% CI 0·88-1·05). There was no significant interaction between SBP and effect of endovascular thrombectomy on functional outcome (p=0·96). INTERPRETATION: In our meta-analysis, high admission SBP was associated with worse functional outcome after stroke, but SBP did not seem to negate the effect of endovascular thrombectomy. This finding suggests that admission SBP should not form the basis for decisions to withhold or delay endovascular thrombectomy for ischaemic stroke, but randomised trials are needed to further investigate this possibility. FUNDING: Medtronic.

Automated segmentation of cerebral vasculature with aneurysms in 3DRA and TOF-MRA using geodesic active regions: an evaluation study.

PURPOSE: To evaluate the suitability of an improved version of an automatic segmentation method based on geodesic active regions (GAR) for segmenting cerebral vasculature with aneurysms from 3D x-ray reconstruction angiography (3DRA) and time of flight magnetic resonance angiography (TOF-MRA) images available in the clinical routine. METHODS: Three aspects of the GAR method have been improved: execution time, robustness to variability in imaging protocols, and robustness to variability in image spatial resolutions. The improved GAR was retrospectively evaluated on images from patients containing intracranial aneurysms in the area of the Circle of Willis and imaged with two modalities: 3DRA and TOF-MRA. Images were obtained from two clinical centers, each using different imaging equipment. Evaluation included qualitative and quantitative analyses of the segmentation results on 20 images from 10 patients. The gold standard was built from 660 cross-sections (33 per image) of vessels and aneurysms, manually measured by interventional neuroradiologists. GAR has also been compared to an interactive segmentation method: isointensity surface extraction (ISE). In addition, since patients had been imaged with the two modalities, we performed an intermodality agreement analysis with respect to both the manual measurements and each of the two segmentation methods. RESULTS: Both GAR and ISE differed from the gold standard within acceptable limits compared to the imaging resolution. GAR (ISE) had an average accuracy of 0.20 (0.24) mm for 3DRA and 0.27 (0.30) mm for TOF-MRA, and had a repeatability of 0.05 (0.20) mm. Compared to ISE, GAR had a lower qualitative error in the vessel region and a lower quantitative error in the aneurysm region. The repeatability of GAR was superior to manual measurements and ISE. The intermodality agreement was similar between GAR and the manual measurements. CONCLUSIONS: The improved GAR method outperformed ISE qualitatively as well as quantitatively and is suitable for segmenting 3DRA and TOF-MRA images from clinical routine.

Cerebral Aneurysm Occlusion at 12-Month Follow-Up After Flow-Diverter Treatment: Statistical Modeling for V&V With Real-World Data.

Background: Flow-Diverter (FD) porosity has been pointed as a critical factor in the occlusion of cerebral aneurysms after treatment. Objective: Verification and Validation of computational models in terms of predictive capacity, relating FD porosity and occlusion after cerebral aneurysms treatment. Methods: Sixty-four aneurysms, with pre-treatment and follow-up images, were considered. Patient demographics and aneurysm morphological information were collected. The computational simulation provided by ANKYRAS provided FD porosity, expansion, and mesh angle. FD occlusion was assessed and recorded from follow-up images. Multiple regression Logit and analysis of covariance (ANCOVA) models were used to model the data with both categorical and continuous models. Results: Occlusion of the aneurysm after 12 months was affected by aneurysm morphology but not by FD mesh morphology. A Time-To-Occlusion (TTO) of 6.92 months on average was observed with an SE of 0.24 months in the aneurysm population surveyed. TTO was estimated with statistical significance from the resulting model for the data examined and was capable of explaining 92% of the data variation. Conclusions: Porosity was found to have the most correction power when assessing TTO, proving its importance in the process of aneurysm occlusion. Still, further Verification and Validation (V&V) of treatment simulation in more extensive, multi-center, and randomized databases is required.

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry.

BACKGROUND AND PURPOSE:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. METHODS:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). RESULTS:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). CONCLUSIONS:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Transfer to the Local Stroke Center versus Direct Transfer to Endovascular Center of Acute Stroke Patients with Suspected Large Vessel Occlusion in the Catalan Territory (RACECAT): Study protocol of a cluster randomized within a cohort trial.

RATIONALE: Optimal pre-hospital delivery pathways for acute stroke patients suspected to harbor a large vessel occlusion have not been assessed in randomized trials. AIM: To establish whether stroke subjects with rapid arterial occlusion evaluation scale based suspicion of large vessel occlusion evaluated by emergency medical services in the field have higher rates of favorable outcome when transferred directly to an endovascular center (endovascular treatment stroke center), as compared to the standard transfer to the closest local stroke center (local-SC). DESIGN: Multicenter, superiority, cluster randomized within a cohort trial with blinded endpoint assessment. PROCEDURE: Eligible patients must be 18 or older, have acute stroke symptoms and not have an immediate life threatening condition requiring emergent medical intervention. They must be suspected to have intracranial large vessel occlusion based on a pre-hospital rapid arterial occlusion evaluation scale of ≥5, be located in geographical areas where the default health authority assigned referral stroke center is a non-thrombectomy capable hospital, and estimated arrival at a thrombectomy capable stroke hospital in less than 7 h from time last seen well. Cluster randomization is performed according to a pre-established temporal sequence (temporal cluster design) with three strata: day/night, distance to the endovascular treatment stroke center, and week/week-end day. STUDY OUTCOME: The primary endpoint is the modified Rankin Scale score at 90 days. The primary safety outcome is mortality at 90 days. ANALYSIS: The primary endpoint based on the modified intention-to-treat population is the distribution of modified Rankin Scale scores at 90 days analyzed under a sequential triangular design. The maximum sample size is 1754 patients, with two planned interim analyses when 701 (40%) and 1227 patients have completed follow-up. Hypothesized common odds ratio is 1.35.

Mediation of the Relationship Between Endovascular Therapy and Functional Outcome by Follow-up Infarct Volume in Patients With Acute Ischemic Stroke.

Importance: The positive treatment effect of endovascular therapy (EVT) is assumed to be caused by the preservation of brain tissue. It remains unclear to what extent the treatment-related reduction in follow-up infarct volume (FIV) explains the improved functional outcome after EVT in patients with acute ischemic stroke. Objective: To study whether FIV mediates the relationship between EVT and functional outcome in patients with acute ischemic stroke. Design, Setting, and Participants: Patient data from 7 randomized multicenter trials were pooled. These trials were conducted between December 2010 and April 2015 and included 1764 patients randomly assigned to receive either EVT or standard care (control). Follow-up infarct volume was assessed on computed tomography or magnetic resonance imaging after stroke onset. Mediation analysis was performed to examine the potential causal chain in which FIV may mediate the relationship between EVT and functional outcome. A total of 1690 patients met the inclusion criteria. Twenty-five additional patients were excluded, resulting in a total of 1665 patients, including 821 (49.3%) in the EVT group and 844 (50.7%) in the control group. Data were analyzed from January to June 2017. Main Outcome and Measure: The 90-day functional outcome via the modified Rankin Scale (mRS). Results: Among 1665 patients, the median (interquartile range [IQR]) age was 68 (57-76) years, and 781 (46.9%) were female. The median (IQR) time to FIV measurement was 30 (24-237) hours. The median (IQR) FIV was 41 (14-120) mL. Patients in the EVT group had significantly smaller FIVs compared with patients in the control group (median [IQR] FIV, 33 [11-99] vs 51 [18-134] mL; P = .007) and lower mRS scores at 90 days (median [IQR] score, 3 [1-4] vs 4 [2-5]). Follow-up infarct volume was a predictor of functional outcome (adjusted common odds ratio, 0.46; 95% CI, 0.39-0.54; P < .001). Follow-up infarct volume partially mediated the relationship between treatment type with mRS score, as EVT was still significantly associated with functional outcome after adjustment for FIV (adjusted common odds ratio, 2.22; 95% CI, 1.52-3.21; P < .001). Treatment-reduced FIV explained 12% (95% CI, 1-19) of the relationship between EVT and functional outcome. Conclusions and Relevance: In this analysis, follow-up infarct volume predicted functional outcome; however, a reduced infarct volume after treatment with EVT only explained 12% of the treatment benefit. Follow-up infarct volume as measured on computed tomography and magnetic resonance imaging is not a valid proxy for estimating treatment effect in phase II and III trials of acute ischemic stroke.

Early Results in Flow Diverter Sizing by Computational Simulation: Quantification of Size Change and Simulation Error Assessment.

BACKGROUND: Sizing of flow diverters (FDs) stent in the treatment of intracranial aneurysms is a challenging task due to the change of stent length after implantation. OBJECTIVE: To quantify the size change and assess the error in length prediction in 82 simulated FD deployments. METHODS: Eighty-two consecutive patients treated with FDs were retrospectively analyzed. Implanted FD length was measured from angiographic images and compared to the nominal sizes of the implanted device. Length change was obtained by subtracting the nominal length from the real length and dividing by the nominal length. Implanted devices were simulated on 3-dimensional models of each patient. Simulation error was obtained by subtracting real length from simulated length and dividing by the real length of the FD. Subanalysis was done using ANOVA. Statistical significance was set to P < .05, and bootstrap resampling was used. RESULTS: When assessing the length change of the FD after implantation, changes of 30% in average and up to 80% with reference to the nominal length of the device were observed. The simulation results showed a lower error of 3.52% in average with a maximum of 30%. Paired t-test showed nonsignificant differences between measured and real length (P = .07, with the mean of differences at 0.45 mm, 95% confidence interval [-0.950 0.038]). CONCLUSION: Nominal length is not an accurate sizing metric when choosing the size of an FD irrespective of the brand and manufacturer. Good estimation of the final length of the stent after deployment as expressed by an error of 3.5% in average.

Imaging features and safety and efficacy of endovascular stroke treatment: a meta-analysis of individual patient-level data.

BACKGROUND: Evidence regarding whether imaging can be used effectively to select patients for endovascular thrombectomy (EVT) is scarce. We aimed to investigate the association between baseline imaging features and safety and efficacy of EVT in acute ischaemic stroke caused by anterior large-vessel occlusion. METHODS: In this meta-analysis of individual patient-level data, the HERMES collaboration identified in PubMed seven randomised trials in endovascular stroke that compared EVT with standard medical therapy, published between Jan 1, 2010, and Oct 31, 2017. Only trials that required vessel imaging to identify patients with proximal anterior circulation ischaemic stroke and that used predominantly stent retrievers or second-generation neurothrombectomy devices in the EVT group were included. Risk of bias was assessed with the Cochrane handbook methodology. Central investigators, masked to clinical information other than stroke side, categorised baseline imaging features of ischaemic change with the Alberta Stroke Program Early CT Score (ASPECTS) or according to involvement of more than 33% of middle cerebral artery territory, and by thrombus volume, hyperdensity, and collateral status. The primary endpoint was neurological functional disability scored on the modified Rankin Scale (mRS) score at 90 days after randomisation. Safety outcomes included symptomatic intracranial haemorrhage, parenchymal haematoma type 2 within 5 days of randomisation, and mortality within 90 days. For the primary analysis, we used mixed-methods ordinal logistic regression adjusted for age, sex, National Institutes of Health Stroke Scale score at admission, intravenous alteplase, and time from onset to randomisation, and we used interaction terms to test whether imaging categorisation at baseline modifies the association between treatment and outcome. This meta-analysis was prospectively designed by the HERMES executive committee but has not been registered. FINDINGS: Among 1764 pooled patients, 871 were allocated to the EVT group and 893 to the control group. Risk of bias was low except in the THRACE study, which used unblinded assessment of outcomes 90 days after randomisation and MRI predominantly as the primary baseline imaging tool. The overall treatment effect favoured EVT (adjusted common odds ratio [cOR] for a shift towards better outcome on the mRS 2·00, 95% CI 1·69-2·38; p<0·0001). EVT achieved better outcomes at 90 days than standard medical therapy alone across a broad range of baseline imaging categories. Mortality at 90 days (14·7% vs 17·3%, p=0·15), symptomatic intracranial haemorrhage (3·8% vs 3·5%, p=0·90), and parenchymal haematoma type 2 (5·6% vs 4·8%, p=0·52) did not differ between the EVT and control groups. No treatment effect modification by baseline imaging features was noted for mortality at 90 days and parenchymal haematoma type 2. Among patients with ASPECTS 0-4, symptomatic intracranial haemorrhage was seen in ten (19%) of 52 patients in the EVT group versus three (5%) of 66 patients in the control group (adjusted cOR 3·94, 95% CI 0·94-16·49; pinteraction=0·025), and among patients with more than 33% involvement of middle cerebral artery territory, symptomatic intracranial haemorrhage was observed in 15 (14%) of 108 patients in the EVT group versus four (4%) of 113 patients in the control group (4·17, 1·30-13·44, pinteraction=0·012). INTERPRETATION: EVT achieves better outcomes at 90 days than standard medical therapy across a broad range of baseline imaging categories, including infarcts affecting more than 33% of middle cerebral artery territory or ASPECTS less than 6, although in these patients the risk of symptomatic intracranial haemorrhage was higher in the EVT group than the control group. This analysis provides preliminary evidence for potential use of EVT in patients with large infarcts at baseline. FUNDING: Medtronic.

Transoral ultrasonic surgery of pharyngolaryngeal giant hemangioma after ethylene-vinyl alcohol copolymer (Onyx) embolization.

BACKGROUND: Cervico-mediastinal hemangiomas in adulthood are rare and slow-growing vascular tumors. The optimal treatment for giant hemangiomas is controversial. In asymptomatic cases, clinical observation is generally recommended. METHODS: We report the transoral resection of a pharyngolaryngeal hemangioma (diameters of 44 × 56 × 39 mm) with tracheal involvement and mediastinal extension. Clinically, the patient had throat foreign body sensation, severe dyspnea and stridor. The hemangioma was first embolized by injecting ethylene-vinyl alcohol copolymer (Onyx) transorally, and then the obstructive aspect of the tumor was resected with a bipolar and ultrasonic clamp (ThunderBeat®, Olympus). RESULTS: Two months after surgery, nasal fiberendoscopy showed complete disappearance of the vascular mass at the larynx and hypopharynx, with a normal mobility of the larynx. CONCLUSION: In symptomatic patients, surgical reduction of large pharyngolaryngeal hemangiomas may be feasible by direct embolization and transoral ultrasonic resection. Both may provide an almost bloodless surgical field. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1239-1242, 2017.

Complete reperfusion is required for maximal benefits of mechanical thrombectomy in stroke patients.

A mTICI 2b or a mTICI 3 score are currently considered success following mechanical thrombectomy (MT) in acute stroke but is undetermined whether the two scores translate equivalent outcomes. We present a single-center, retrospective cohort of patients with anterior circulation stroke treated with MT and achieving a final mTICI score 2b or 3. A multimodal CT at baseline and a multimodal MRI at 24 hours assessed the growth of the infarct, and the modified Rankin Scale (mRS) assessed functional outcome at 90 days. The primary outcome was the shift analysis of the mRS at day 90 in ordinal regression adjusted for covariates (age, sex, pretreatment NIHSS score, target occlusion, infarct core, pretreatment alteplase), and the collateral score. Infarct growth was explored in a similarly adjusted multiple linear regression model. MT was started within a median of 285 minutes of symptom onset; 51 (41%) patients achieved a mTICI 2b, and 74 (59%), a mTICI 3. mTICI 3 resulted in better mRS score transitions than mTICI 2b (odds ratio 2.018 [95% CI 1.033-3.945], p = 0. 040), and reduced infarct growth (p = 0.002). We conclude that in patients with acute stroke receiving MT, success should be redefined as achieving a mTICI 3 score.

Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial.

BACKGROUND: The REVASCAT trial and other studies have shown that the neurovascular thrombectomy improves outcomes at 90 days post stroke. However, whether the observed benefit is sustained in the long term remains unknown. We report the results of the prespecified 12-month analysis of the REVASCAT trial. METHODS: Patients with acute ischaemic stroke who could be treated within 8 h of symptom onset were randomly assigned to medical therapy (including intravenous alteplase when eligible) and neurovascular thrombectomy with Solitaire FR or medical therapy alone. The main secondary outcome measure at 1 year follow-up was disability, measured using the modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death) with categories 5 (severe disability) and 6 (death) collapsed into one category (severe disability or death), analysed as the distribution of the mRS. Additional prespecified secondary outcome measures included health-related quality of life measured with the EuroQol five dimensions questionnaire (EQ-5D) utility index (ranging from -0·3 to 1, higher values indicate better quality of life), the rate of functional independence (mRS 0-2), and cognitive function measured with the Trail Making Test (reported elsewhere). Treatment allocation was open label but endpoints at 12 months were assessed by masked investigators. The trial was registered at ClinicalTrials.gov, number NCT01692379. FINDINGS: From Nov 24, 2012, to Dec 12, 2014, 206 patients were randomly assigned to medical therapy plus endovascular treatment (n=103) or medical treatment alone (n=103), at four centres in Catalonia, Spain. At 12 months post randomisation, based on 205 of 206 outcomes available at 12 months, thrombectomy reduced disability over the range of the mRS (common adjusted odds ratio [aOR] 1·80, 95% CI 1·09-2·99), and improved functional independence (mRS=0-2; 45 [44%] of 103 patients vs 31 [30%] of 103 patients; aOR 1·86, 95% CI 1·01-3·44). Health-related quality of life was superior in the thrombectomy group (mean EQ-5D utility index score, 0·46 [SD 0·38] in the thrombectomy group vs 0·33 [0·33] in the control group, difference 0·12 [95% CI 0·03-0·22]; p=0·01). 1-year mortality was 23% (24 of 103 patients) in the thrombectomy group versus 24% (25 of 103 patients) in the control group. INTERPRETATION: At 12 months follow-up, neurovascular thrombectomy reduced post-stroke disability and improved health-related quality of life, indicating sustained benefit. These findings have important clinical and public health implications for evaluating the cost-effectiveness of the intervention in the long term. FUNDING: Fundació Ictus Malaltia Vascular through an unrestricted grant from Medtronic.

Mechanical thrombectomy in acute basilar artery occlusion: A safety and efficacy single centre study.

OBJECTIVES: The objective of this study was to add more evidence about the efficacy and safety of mechanical thrombectomy in patients with basilar artery occlusion and secondarily to identify prognostic factors. METHODS: Twenty-two consecutive patients (mean age 60.5 years, 15 men) with basilar artery occlusion treated with mechanical thrombectomy were included. Clinical, procedure and radiological data were collected. Primary outcomes were the modified Rankin scale score with a good outcome defined by a modified Rankin scale score of 0-2 and mortality rate at three months. RESULTS: The median National Institutes of Health stroke scale at admission was 24 (interquartile range 11.5-31.25). Twelve patients (54.5%) required tracheal intubation due to a decreased level of consciousness. Successful recanalisation (modified treatment in cerebral ischaemia scale 2b-3) was achieved in 20 patients (90.9%). A favourable clinical outcome (modified Rankin scale score 0-2) was observed in nine patients (40.9%) and the overall mortality rate was 40.9% (nine patients). Haemorrhagic events were observed in three patients (13.63%). A decreased level of consciousness requiring intubation in the acute setting was more frequent in patients with poor outcomes (84.6%) than in patients with favourable outcomes (11.1%), and in patients who died (100%) compared with those who survived (23.1%), with a statistically significant difference (P = 0.002 and P = 0.001, respectively). CONCLUSION: Mechanical thrombectomy is feasible and effective in patients with acute basilar artery occlusion. A decreased level of consciousness requiring tracheal intubation seems to be a prognostic factor and is associated with a poor clinical outcome and higher mortality rate. These initial results must be confirmed by further prospective studies with a larger number of patients.

Diabetes-induced changes in the 5-hydroxytryptamine inhibitory receptors involved in the pressor effect elicited by sympathetic stimulation in the pithed rat.

1. We investigated the effect of alloxan-induced diabetes on the inhibitory mechanisms of 5-hydroxytryptamine (5-HT) in the pressor responses induced by stimulation of sympathetic vasopressor outflow in pithed rats, and analysed the type and/or subtype of 5-HT receptors involved. 2. Diabetes was induced in male Wistar rats by a single s.c. injection of alloxan, then 4 weeks later, they were anaesthetized, pretreated with atropine and pithed. Electrical stimulation of the sympathetic outflow from the spinal cord (0.1, 0.5, 1 and 5 Hz) resulted in frequency-dependent increases in blood pressure. 3. Intravenous infusions of 5-HT (1-80 microg kg(-1) min(-1)) reduced the pressor effects obtained by electrical stimulation. The 5-HT(1) receptor agonist 5-carboxamidotryptamine, 5-CT (5 microg kg(-1) min(-1)), caused an inhibition of the pressor response, whereas the selective 5-HT(2) receptor agonist, alpha-methyl-5-HT (5 microg kg(-1) min(-1)) and the selective 5-HT(3) receptor agonist, 1-phenylbiguanide (40 microg kg(-1) min(-1)), did not modify the sympathetic pressor responses. 5-HT had no effect on exogenous noradrenaline (NA)-induced pressor responses. 4. The inhibition of electrically induced pressor responses by 5-HT (10 microg kg(-1) min(-1)) was unable to be elicited after i.v. treatment with methiothepin (100 microg kg(-1)) because of the marked inhibition produced by methiothepin alone. The 5-HT-induced inhibition was blocked after i.v. administration of WAY-100,635 (100 microg kg(-1)) and not affected by ritanserin (1 mg kg(-1)), MDL 72222 (2 mg kg(-1)). 5. The selective 5-HT(1A) receptor agonist, 8-hydroxydipropylaminotretalin hydrobromide (8-OH-DPAT) (5-20 microg kg(-1) min(-1)) but neither the rodent 5-HT(1B) receptor agonist, CGS-12066B (5 microg kg(-1) min(-1)), nor the selective nonrodent 5-HT(1B) and 5-HT(1D) receptor agonist, L-694,247 (5 and 40 microg kg(-1) min(-1)), inhibited the electrically induced pressor response. The selective 5-HT(1A) receptor antagonist, WAY-100,635 (100 microg kg(-1)), blocked the inhibition induced by 8-OH-DPAT (10 microg kg(-1) min(-1)). 8-OH-DPAT had no effect on exogenous NA-induced pressor responses. 6. Experimental diabetes produces changes in the inhibitory effect induced by 5-HT on electrically induced sympathetic pressor responses, such that the inhibitory action induced by 5-HT in diabetic pithed rats is mediated by prejunctional 5-HT(1A) receptors.

Computation of the change in length of a braided device when deployed in realistic vessel models.

PURPOSE: An important issue in the deployment of braided stents, such as flow diverters, is the change in length, also known as foreshortening, underwent by the device when is released from the catheter into a blood vessel. The position of the distal end is controlled by the interventionist, but knowing a priori the position of the proximal end of the device is not trivial. In this work, we assess and validate a novel computer method to predict the length that a braided stent will adopt inside a silicon model of an anatomically accurate vessel. METHODS: Three-dimensional rotational angiography images of aneurysmatic patients were used to generate surface models of the vessels (3D meshes) and then create accurate silicon models from them. A braided stent was deployed into each silicon model to measure its length. The same stents deployed on the silicon models were virtually deployed on the 3D meshes using the method being evaluated. RESULTS: The method was applied to five stent placements on three different silicon models. The length adopted by the real braided device in the silicon models varies between 15 and 30% from the stent length specified by the manufacturer. The final length predicted by the method was within the estimated error of the measured real stent length. CONCLUSIONS: The method provides, in a few seconds, the length of a braided stent deployed inside a vessel, showing an accurate estimation of the final length for the cases studied. This technique could provide useful information for planning the intervention and improve endovascular treatment of intracranial aneurysms in the future.